Cancer Is Partly Caused By Bad Luck, Study Finds

Nearly two-thirds of cell mutations that cause cancer are caused by random error, a study found.

Steve Gschmeissner
/ Science Source

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Originally published on March 24, 2017 2:17 pm

Cancer can be caused by tobacco smoke or by an inherited trait, but new research finds that most of the mutations that lead to cancer crop up naturally.

The authors of the study published Thursday poked a hornet's nest by suggesting that many cancers are unavoidable.

The provocative findings by Bert Vogelstein and Cristian Tomasetti at the Johns Hopkins Kimmel Cancer Center, have stirred up a heated scientific debate that started two years ago, when they published a report along similar lines.

Back then, critics said they were undercutting important messages about cancer prevention. So when these scientists had new results to report, Vogelstein addressed that concern head-on.

"We all agree that 40 percent of cancers are preventable," he said at a news conference. "The question is, what about the other cancers that aren't known to be preventable?"

Vogelstein, who is also an investigator with the Howard Hughes Medical Institute, explained how he and Tomasetti have refined that question. He notes that every time a perfectly normal cell divides, it makes several mistakes when it copies its DNA. These are naturally occurring mutations.

Most of the time, those mutations are in unimportant bits of DNA. That's good luck. "But occasionally they occur in a cancer driver gene. That's bad luck," Vogelstein says.

After two or three of these driver genes get mutated in the same cell, they can transform that healthy cell into a cancer cell.

In their new paper in Science, the researchers set out to quantify how often those random errors are an inevitable part of cell division, how often they're caused by nasty chemicals like tobacco smoke and how often they're inherited.

The answer: 66 percent of the total mutations are random, about 29 percent are due to the environment and the remaining five percent are due to heredity.

These numbers vary depending on the type of cancer, they found.

Lung cancer is largely the result of environmental causes, while the vast majority of childhood cancer is a result of these bad-luck mutations, they found.

Vogelstein says parents often think they, somehow, are responsible for their child's cancer, but that is not the case. "They need to understand that these cancers would have happened no matter what they did," he says. "We don't need to add guilt to an already tragic situation."

Of course, people can reduce their risk of preventable cancer by avoiding tobacco, eating well and maintaining a healthy body weight. But the bad news is that most mutations arise naturally.

So, what can people do? "Nothing. Right now, nothing," Vogelstein says.

But, he's hopeful that if scientists focus on that question, they will have a more encouraging answer someday.

Even without an action plan, the question of how much human cancer is caused by bad luck and how much is caused by bad things we do "is super fascinating," says Martin Nowak, a biologist and mathematician at Harvard who wrote a commentary about the study for Science.

He says the findings are stirring up the field, and that's a good thing.

"It's very unclear to me about whether we have the tools to answer these questions," he says. And, rather than settling the controversy raised by the scientists' previous paper, "I think it will raise an even bigger controversy," Nowak says.

One of the new sticking points is that mutations, while necessary for cancer to develop, aren't the whole story. For example, some scientists say the study doesn't fully account for how hormones can influence cancer.

Dr. Graham Colditz, an epidemiologist at Washington University in St. Louis isn't convinced that hazards can been neatly sorted into the categories of hereditary, environmental and unavoidable mutations. "How these interplay with each other, I think is potentially more complex," he says.

Vogelstein and Tomasetti agree on that point. The causes of cancer are complex.

"We're not saying the only thing that determines the seriousness of the cancer, or its aggressiveness, or its likelihood to cause the patient's death, are these mutations," Vogelstein tells Shots. "We're simply saying that they are necessary to get the cancer."

Copyright 2017 NPR. To see more, visit http://www.npr.org/.

KELLY MCEVERS, HOST:

There are a lot of reasons why people get cancer. Sometimes it's exposure to something toxic like smoke. Sometimes it's just bad genes. New research finds most of the genetic mutations that lead to cancer crop up naturally, and they're unavoidable. NPR's Richard Harris reports.

RICHARD HARRIS, BYLINE: First the backstory - two years ago, Bert Vogelstein and Cristian Tomasetti at Johns Hopkins University started controversy by suggesting that many cancers are unavoidable. Critics said that was undercutting the message that many cancers are preventable. So when these scientists had new results to report, Vogelstein made that point absolutely clear.

(SOUNDBITE OF PRESS CONFERENCE)

BERT VOGELSTEIN: We all agree that 40 percent of cancers are preventable. The question is, what about the other cancers that aren't known to be preventable?

HARRIS: Speaking at a news conference, Dr. Vogelstein and his colleague explained how they have now refined that question.

(SOUNDBITE OF PRESS CONFERENCE)

VOGELSTEIN: Every time a perfectly normal cell divides, it makes several mistakes, mutations.

HARRIS: Most of the time, those mutations are in unimportant bits of DNA. That's good luck.

(SOUNDBITE OF PRESS CONFERENCE)

VOGELSTEIN: But occasionally they occur in a cancer driver gene. That's bad luck.

HARRIS: After two or three of these driver genes get mutated in the same cell, the cell can turn cancerous. In their new paper in Science, the researchers set out to quantify how often these mutations are random errors that result from cell division, how often they're caused by nasty chemicals like tobacco smoke and how often they're inherited.

(SOUNDBITE OF PRESS CONFERENCE)

VOGELSTEIN: Sixty-six percent of the total mutations are random, about 29 percent due to the environment and the remaining 5 percent due to heredity.

HARRIS: These numbers depend on the type of cancer. Lung cancer is largely triggered by environmental causes - smoking - while the vast majority of childhood cancer is a result of these bad luck mutations. Right now, Vogelstein says parents who focus on environment and heredity are likely to think they are somehow responsible for their child's disease - not so.

(SOUNDBITE OF PRESS CONFERENCE)

VOGELSTEIN: They need to understand that these cancers would have occurred no matter what they did. We don't need to add guilt to an already tragic situation.

HARRIS: Of course people can reduce their risk of preventable cancer by avoiding tobacco and eating well. As for the mutations that occur spontaneously...

(SOUNDBITE OF PRESS CONFERENCE)

VOGELSTEIN: Now, what can people do - nothing - right now, nothing. This is a question for research.

HARRIS: In fact the paper raises many questions. Martin Novak is a biologist and mathematician at Harvard.

MARTIN NOVAK: The question is super fascinating. So the question is really, how much of human cancer is caused by bad luck? How much is caused by bad things that we do? The question is super fascinating.

HARRIS: He says the new findings are provoking discussion among cancer scientists, and that's all for the good.

NOVAK: How exactly we can actually answer these questions? It is very unclear to me whether we have the tools in hand right now.

HARRIS: So you don't expect this paper to put to rest the controversy that the first one stirred up.

NOVAK: No, I think it will raise an even bigger controversy.

HARRIS: One of the big sticking point is that mutations, while necessary, aren't the whole story. Dr. Graham Colditz at Washington University in St. Louis isn't convinced that hazards have been neatly sorted into the categories of heredity, environment and unavoidable mutations.

GRAHAM COLDITZ: How these interplay with each other I think is still potentially more complex.

HARRIS: Vogelstein and Tomasson (ph) are prepared to argue these matters with their colleagues, and on one point at least they do agree. While mutations are necessary for cancer, they don't entirely explain why some mutated cells eventually become aggressive, deadly cancers and others don't. Richard Harris, NPR News.